Open AccessRNF 168 facilitates proliferation and invasion of esophageal carcinoma, possibly via stabilizing STAT 1
Author(s) -
Yu Na,
Xue Min,
Wang Weilong,
Xia Dongxue,
Li Yajie,
Zhou Xiaofeng,
Pang Dan,
Lu Kui,
Hou Jinghan,
Zhang Aijia,
Zhuang Ting,
Wang Lidong,
Chang Tingmin,
Li Xiumin
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14063
Subject(s) - stat , cancer research , biology , cancer , malignancy , cell growth , cancer cell , signal transduction , microbiology and biotechnology , stat3 , genetics
Oesophageal cancer ranks as one of the most common malignancy in China and worldwide. Although genome‐wide association studies and molecular biology studies aim to elucidate the driver molecules in oesophageal cancer progression, the detailed mechanisms remain to be identified. Interestingly, RNF 168 ( RING finger protein 168) shows a high frequency of gene amplification in oesophageal cancer from TCGA database. Here, we report an important function for RNF 168 protein in supporting oesophageal cancer growth and invasion by stabilizing STAT 1 protein. RNF 168 gene is amplified in oesophageal cancer samples, which tends to correlate with poor prognosis. Depletion RNF 168 causes decreased cell proliferation and invasion in oesophageal cancer cells. Through unbiased RNA sequencing in RNF 168 depleted oesophageal cancer cell, we identifies JAK ‐ STAT pathway is dramatically decreased. Depletion RNF 168 reduced JAK ‐ STAT target genes, such as IRF 1, IRF 9 and IFITM 1. Immuno‐precipitation reveals that RNF 168 associates with STAT 1 in the nucleus, stabilizing STAT 1 protein and inhibiting its poly‐ubiquitination and degradation. Our study provides a novel mechanism that RNF 168 promoting JAK ‐ STAT signalling in supporting oesophageal cancer progression. It could be a promising strategy to target RNF 168 for oesophageal cancer treatment.